Halozyme Therapeutics Profile
Halozyme Therapeutics, Inc. operates as a biopharmaceutical company advancing disruptive solutions to improve patient experiences and outcomes for emerging and established therapies.
As the innovators of ENHANZE drug delivery technology (‘ENHANZE’) with the company’s proprietary enzyme rHuPH20, the company’s commercially-validated solution is used to facilitate the subcutaneous (‘SC’) delivery of injected drugs and fluids, with the intention of reducing the treatment burden for patients. The company licenses its technology to biopharmaceutical companies to collaboratively develop products that combine ENHANZE with the company’s partners’ proprietary compounds. The company also develops, manufactures and commercializes, for itself or with the company’s partners, drug-device combination products using the company’s advanced auto-injector technologies that are designed to provide commercial or functional advantages, such as improved convenience, reliability and tolerability, and enhanced patient comfort and adherence.
The company’s ENHANZE partners’ approved products and product candidates are based on rHuPH20, the company’s patented recombinant human hyaluronidase enzyme. rHuPH20 works by breaking down hyaluronan (‘HA’), a naturally occurring carbohydrate that is a major component of the extracellular matrix of the SC space. This temporarily reduces the barrier to bulk fluid flow allowing for improved and more rapid SC delivery of high dose, high volume injectable biologics, such as monoclonal antibodies and other large therapeutic molecules, as well as small molecules and fluids. The company refers to the application of rHuPH20 to facilitate the delivery of other drugs or fluids as ENHANZE. The company licenses the ENHANZE technology to form collaborations with biopharmaceutical companies that develop or market drugs requiring or benefiting from injection via the SC route of administration. In the development of proprietary intravenous (‘IV’) drugs combined with the company’s ENHANZE technology, data have been generated supporting the potential for ENHANZE to reduce patient treatment burden, as a result of shorter duration of SC administration with ENHANZE compared to IV administration. ENHANZE may enable fixed-dose SC dosing compared to weight-based dosing typically required for IV administration, extend the dosing interval for drugs that are already administered subcutaneously and potentially allow for lower rates of infusion-related reactions. ENHANZE may enable more flexible treatment options, such as home administration by a healthcare professional or potentially the patient or caregiver. Lastly, certain proprietary drugs co-formulated with ENHANZE have been granted additional exclusivity, extending the patent life of the product beyond the patent expiry of the proprietary IV drug.
The company has ENHANZE collaborations and licensing agreements with F. Hoffmann-La Roche, Ltd. and Hoffmann-La Roche, Inc. (‘Roche’), Takeda Pharmaceuticals International AG and Baxalta US Inc. (‘Takeda’), Pfizer Inc. (‘Pfizer’), Janssen Biotech, Inc. (‘Janssen’), AbbVie, Inc. (‘AbbVie’), Eli Lilly and Company (‘Lilly’), Bristol Myers Squibb Company (‘BMS’), argenx BVBA (‘argenx’), ViiV Healthcare (the global specialist HIV Company majority owned by GlaxoSmithKline) (‘ViiV’), Chugai Pharmaceutical Co., Ltd (‘Chugai’) and Acumen Pharmaceuticals, Inc. (‘Acumen’). In addition to receiving upfront licensing fees from the company’s ENHANZE collaborations, the company is entitled to receive event and sales-based milestone payments, revenues from the sale of bulk rHuPH20 and royalties from commercial sales of approved partner products co-formulated with ENHANZE. The company earns royalties from four of these collaborations, including royalties from sales of one product from the Takeda collaboration, four products from the Roche collaboration, one product from the Janssen collaboration and one product from the argenx collaboration.
The company has commercialized auto-injector products with several pharmaceutical companies, including Teva Pharmaceutical Industries, Ltd. (‘Teva’) and Otter Pharmaceuticals, LLC (‘Otter’). The company has development programs including auto-injectors with Idorsia Pharmaceuticals Ltd. (‘Idorsia’).
The company’s commercial portfolio of proprietary products includes Hylenex, utilizing rHuPH20, and the company’s specialty product XYOSTED, utilizing its auto-injector technology.
Strategy
The company is a leader in converting IV biologics to SC delivery and extending the dosing interval of SC drugs, using the company’s commercially-validated ENHANZE technology. The company’s ENHANZE technology also has the potential for SC delivery of small molecules and other therapeutic modalities, including those developed as long-acting injectables and other therapies that might benefit from larger dose/larger volume SC delivery. The company collaborates with leading pharmaceutical and biotechnology companies to help them develop products that combine the company’s ENHANZE technology with their proprietary compounds. The company targets large, attractive markets, where ENHANZE-enabled SC delivery has the potential to deliver competitive differentiation and other important benefits to the company’s partners, such as larger injection volumes administered rapidly and extended dosing intervals. In addition, ENHANZE has been demonstrated to enable the combination of two therapeutic antibodies in a single injection, as well as the development of new co-formulation intellectual property. The company leverages its strategic, technical, regulatory and alliance management skills in the support of the company’s partners' efforts to develop new SC delivered products. The company has eleven collaborations with seven approved products and additional product candidates in development using the company’s ENHANZE technology. The company intends to work with its existing partners to expand its collaborations to add new targets and develop targets and product candidates under the terms of the operative collaboration agreements. The company will also continue the company’s efforts to enter into new collaborations to derive additional revenue from the company’s proprietary technology.
The company also supports leading pharmaceutical companies by assisting in the development of, and supplying, auto-injector devices and auto-injector drug combination products. The company leverages its engineering, regulatory and manufacturing skills to support the company’s partners’ plans. The company intends to extend the range of auto-injectors available to current and new partners. In 2023, the company completed a successful Phase I clinical study using a high-volume auto-injector.
Proprietary Products and Product Candidates
Hylenex Recombinant (Hyaluronidase Human Injection)
The company markets and sells Hylenex recombinant which is a formulation of rHuPH20 that facilitates SC administration for achieving hydration, increases the dispersion and absorption of other injected drugs and, in SC urography, to improve resorption of radiopaque agents. Hylenex recombinant is the number one prescribed branded hyaluronidase.
XYOSTED (testosterone enanthate) Injection
The company markets and sells its proprietary product XYOSTED for SC administration of testosterone replacement therapy (‘TRT’) in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadism). XYOSTED is the only Food and Drug Administration (‘FDA’)-approved SC testosterone enanthate product for once-weekly, at-home self-administration and is approved and marketed in the United States (‘U.S.’) in three dosage strengths, 50 mg, 75 mg and 100 mg.
ATRS – 1902
The company has an ongoing program to develop a proprietary drug device combination product for the endocrinology market, for patients who require additional supplemental hydrocortisone, identified as ATRS-1902. The development program uses a novel proprietary auto-injector platform to deliver a liquid stable formulation of hydrocortisone.
In June 2021, the company submitted an investigational new drug (‘IND’) application with the FDA for the initiation of a Phase 1 clinical study of ATRS-1902 for adrenal crisis rescue. The IND application included the protocol for an initial clinical study to compare the pharmacokinetics (‘PK’) profile of the company’s novel formulation of hydrocortisone versus Solu-Cortef, which is an anti-inflammatory glucocorticoid and is the current standard of care for the management of acute adrenal crises.
In July 2021, the FDA accepted the company’s IND for ATRS-1902 enabling the company to initiate its Phase 1 clinical study. The Phase 1 clinical study, designed to evaluate the safety, tolerability and PK of a liquid stable formulation of hydrocortisone, was initiated in September 2021. The study was a cross-over design to establish the PK profile of ATRS-1902 (100 mg) compared to Solu-Cortef (100 mg), the reference-listed drug, in 32 healthy adults.
In January 2022, the company announced the positive results from the Phase 1 clinical study and were granted Fast Track designation by the FDA. The positive results supported the advancement of the company’s ATRS-1902 development program to a pivotal study for the treatment of acute adrenal insufficiency, using the company’s Vai novel proprietary rescue pen platform to deliver a liquid stable formulation of hydrocortisone.
Partnered Products
ENHANZE Collaborations
Roche Collaboration
In December 2006, the company and Roche entered into a collaboration and license agreement under which Roche obtained a worldwide license to develop and commercialize product combinations of rHuPH20 and up to twelve Roche target compounds (the ‘Roche Collaboration’). Under this agreement, Roche elected a total of eight targets, two of which are exclusive.
In September 2013, Roche launched a SC formulation of Herceptin (trastuzumab) (Herceptin SC) in Europe for the treatment of patients with HER2-positive breast cancer followed by launches in additional countries. This formulation utilizes the company’s ENHANZE technology and is administered in two to five minutes, compared to 30 to 90 minutes with the standard IV form. Herceptin SC has since received approval in Canada, the U.S. (under the brand name Herceptin Hylecta) and China.
In June 2020, the FDA approved the fixed-dose combination of Perjeta (pertuzumab) and Herceptin for SC injection (Phesgo) utilizing ENHANZE technology for the treatment of patients with HER2-positive breast cancer. Phesgo has since received approval in Europe and China. In September 2023, Chugai Pharmaceuticals Co., Ltd (a Member of the Roche Group) announced that it had obtained regulatory approval for Phesgo from the Ministry of Health, Labour and Welfare (‘MHLW’) in Japan. The company will receive royalties for Phesgo sales in Japan as part of the company’s licensing agreement with Roche.
In June 2014, Roche launched MabThera SC in Europe for the treatment of patients with common forms of non-Hodgkin lymphoma (‘NHL’), followed by launches in additional countries. This formulation utilizes the company’s ENHANZE technology and is administered in approximately five minutes compared to the approximate 1.5 to 4 hour IV infusion. In May 2016, Roche announced that the European Medicines Agency (‘EMA’) approved MabThera SC to treat patients with chronic lymphocytic leukemia (‘CLL’). In June 2017, the FDA-approved Genentech’s RITUXAN HYCELA, a combination of rituximab using ENHANZE technology (approved and marketed under the MabThera SC brand in countries outside the U.S. and Canada), for CLL and two types of NHL, follicular lymphoma and diffuse large B-cell lymphoma. In March 2018, Health Canada approved a combination of rituximab and ENHANZE (approved and marketed under the brand name RITUXAN SC) for patients with CLL. In November 2022, Roche submitted the independent medical assessment (‘IMA’) for MabThera SC to the Center for Drug Evaluation (‘CDE’) in China.
In September 2017 and October 2018, the company entered into agreements with Roche to develop and commercialize additional exclusive targets using ENHANZE technology. The upfront license payment may be followed by event-based payments subject to Roche’s achievement of specified development, regulatory and sales-based milestones. In addition, Roche will pay royalties to the company if products under the collaboration are commercialized.
In December 2018, Roche initiated a Phase 1b/2 study in patients with non-small cell lung cancer (‘NSCLC’) for TECENTRIQ (atezolizumab) using ENHANZE technology, followed by initiation of a Phase 3 study in December 2020. In August 2022, Roche announced that the Phase 3 study met its co-primary endpoints showing non-inferior levels of Tecentriq in the blood PK, when injected subcutaneously, compared with IV infusion, in cancer immunotherapy-naïve patients with advanced or metastatic NSCLC for whom prior platinum therapy has failed. The safety profile of the SC formulation was consistent with that of IV Tecentriq. In August 2023, Roche announced the approval of Tecentriq SC with ENHANZE by the Medicines and Healthcare products Regulatory Agency (‘MHRA’) in Great Britain. In January 2024, Roche received European Commission (‘EC’) marketing authorization for Tecentriq SC for all approved indications of Tecentriq IV. Roche is expecting Tecentriq SC approval in the U.S. in September 2024 and is planning to launch soon after. Tecentriq SC enables SC delivery in approximately seven minutes, compared with 30-60 minutes for IV infusion.
In August 2019, Roche initiated a Phase 1 study evaluating ocrelizumab SC with ENHANZE technology in subjects with multiple sclerosis, followed by initiation of a Phase 3 study in April 2022. In July 2023, Roche announced that the Phase III OCARINA II trial evaluating ocrelizumab SC with ENHANZE as a twice a year 10-minute SC injection met its primary and secondary endpoints in patients with relapsing forms of multiple sclerosis (‘MS’) or primary progressive MS (‘RMS’ or ‘PPMS’). Subsequently, Roche filed ocrelizumab SC with ENHANZE with regulatory authorities in the EU, the United Kingdom (‘U.K.’) and the U.S.
In October 2019, Roche nominated a new undisclosed exclusive target to be studied using ENHANZE technology. In November 2021, Roche initiated a Phase 1 study with the undisclosed target and ENHANZE.
Takeda Collaboration
In September 2007, the company and Takeda entered into a collaboration and license agreement under which Takeda obtained a worldwide, exclusive license to develop and commercialize product combinations of rHuPH20 with GAMMAGARD LIQUID (HYQVIA) (the ‘Takeda Collaboration’). HYQVIA is indicated for the treatment of primary immunodeficiency disorders associated with defects in the immune system.
In May 2013, the EC granted Takeda marketing authorization in all EU Member States for the use of HYQVIA as replacement therapy for adult patients with primary and secondary immunodeficiencies. Takeda launched HYQVIA in the first EU country in July 2013 and has continued to launch in additional countries. In May 2016, Takeda announced that HYQVIA received a marketing authorization from the EC for a pediatric indication.
In September 2014, HYQVIA was approved by the FDA for the treatment of adult patients with primary immunodeficiency in the U.S. HYQVIA is the first SC immune globulin (‘IG’) treatment approved for adult primary immunodeficiency patients with a dosing regimen requiring only one infusion up to once per month (every three to four weeks) and one injection site per infusion in most patients, to deliver a full therapeutic dose of IG.
In September 2020, Takeda announced that the EMA approved a label update for HYQVIA broadening its use and making it the first and only facilitated SC immunoglobulin replacement therapy in adults, adolescents and children with an expanded range of secondary immunodeficiencies (‘SID’).
In October 2021, Takeda initiated a Phase 1 single-dose, single-center, open-label, three-arm study to assess the tolerability and safety of immune globulin SC (human), 20% solution with ENHANZE (TAK-881) at various infusion rates in healthy adult subjects. In October 2023, Takeda initiated a Phase 2/3 study to evaluate PK, safety, and tolerability of subcutaneous administration of TAK-881 in adult and pediatric participants with Primary Immunodeficiency Diseases (‘PIDD’).
In July 2022, Takeda announced positive topline results from pivotal Phase 3 trial evaluating HYQVIA, for maintenance treatment of chronic inflammatory demyelinating polyneuropathy (‘CIDP’). In June 2023, Takeda announced positive full results from a pivotal Phase 3 trial evaluating HYQVIA for maintenance treatment of CIDP and confirmed regulatory applications were under review in the U.S. and EU for HYQVIA use as a maintenance therapy in adults with stable CIDP. In January 2024, Takeda received FDA and EC approval for HYQVIA for the treatment of CIDP as maintenance therapy to prevent the relapse of neuromuscular disability and impairment in adults.
In April 2023, Takeda announced that the FDA-approved the supplemental Biologics License Application (‘sBLA’) to expand the use of HYQVIA to treat primary immunodeficiency in children. In February 2024, Takeda submitted a New Drug Application in Japan seeking approval for TAK-771, subcutaneous 10% human immunoglobulin with ENHANZE, for the treatment of primary immunodeficiency.
Pfizer Collaboration
In December 2012, the company and Pfizer entered into a collaboration and license agreement, under which Pfizer has the worldwide license to develop and commercialize products combining the company’s rHuPH20 enzyme with Pfizer proprietary biologics in primary care and specialty care indications. Pfizer has elected five targets and has returned two targets.
Janssen Collaboration
In December 2014, the company and Janssen entered into a collaboration and license agreement, under which Janssen has the worldwide license to develop and commercialize products combining the company’s rHuPH20 enzyme with Janssen proprietary biologics directed to up to five targets. Targets may be selected on an exclusive basis. Janssen elected CD38 and initiated several Phase 3 studies, Phase 2 studies and Phase 1 studies of DARZALEX (daratumumab), directed at CD38, using ENHANZE technology in patients with amyloidosis, smoldering myeloma and multiple myeloma.
In May 2020, Janssen launched the commercial sale of DARZALEX FASPRO (DARZALEX utilizing ENHANZE technology) in four regimens across five indications in multiple myeloma patients, including newly diagnosed, transplant-ineligible patients, as well as relapsed or refractory patients. As a fixed-dose formulation, DARZALEX FASPRO can be administered over three to five minutes, significantly less time than DARZALEX IV which requires multi-hour infusions. In June 2020, the company announced that Janssen received European marketing authorization and launched the commercial sale of DARZALEX SC utilizing ENHANZE in the EU. Subsequent to these approvals, Janssen received several additional regulatory approvals for additional indications and patient populations in the U.S., EU, Japan and China. Beginning with the U.S., Janssen has marketing authorization for DARZALEX FASPRO in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant, in combination with bortezomib, cyclophosphamide and dexamethasone (‘D-VCd’) for the treatment of adult patients with newly diagnosed AL amyloidosis, in combination with pomalidomide and dexamethasone (‘D-Pd’) for patients with multiple myeloma after first or subsequent relapse, and in combination with Kyprolis (carfilzomib) and dexamethasone for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. In the EU, Janssen has marketing authorization for DARZALEX SC in combination with D-VCd in newly diagnosed adult patients with AL amyloidosis and in combination with D-Pd in adult patients with relapsed or refractory multiple myeloma. In Japan, Janssen has marketing authorization for the SC formulation of DARZALEX (known as DARZQURO in Japan) for the treatment of multiple myeloma and systemic AL amyloidosis. In China, Janssen has marketing authorization for DARZALEX SC for the treatment of primary light chain amyloidosis, in combination with D-VCd in newly diagnosed patients. In January 2024, Janssen announced submission of a sBLA to the FDA seeking approval of a new indication for DARZALEX FASPRO in combination with bortezomib, lenalidomide and dexamethasone (‘D-VRd’) for induction and consolidation treatment and with lenalidomide (‘D-R’) for maintenance treatment of adult patients who are newly diagnosed with multiple myeloma (‘NDMM’) and are eligible for autologous stem cell transplant (‘ASCT’).
In December 2019, Janssen elected EGFR and cMET as a bispecific antibody (amivantamab) target on an exclusive basis, which is being studied in solid tumors. In September 2022, following a Phase 1 study, Janssen initiated a Phase 3 study of lazertinib and amivantamab with ENHANZE in patients with epidermal growth factor receptor (‘EGFR’)-mutated advanced or metastatic non-small cell lung cancer (PALOMA-3). In November 2022, Janssen initiated a Phase 2 study of amivantamab with ENHANZE in multiple regimens in patients with advanced or metastatic solid tumors, including EGFR-mutated non-small cell lung cancer (PALOMA-2). In January 2024, Janssen noted its intention to submit applications in the U.S. and EU seeking approval of a SC formulation for amivantamab SC during 2024.
In July 2021, Janssen elected the target HIV reverse transcriptase limited to non-nucleoside reverse transcriptase inhibitors. In December 2021, Janssen initiated a Phase 1 clinical trial combining rilpivirine and ENHANZE. In 2023, Janssen discontinued the rilpivirine program with ENHANZE.
AbbVie Collaboration
In June 2015, the company and AbbVie entered into a collaboration and license agreement, under which AbbVie has the worldwide license to develop and commercialize products combining the company’s rHuPH20 enzyme with AbbVie proprietary biologics directed to up to nine targets. Targets may be selected on an exclusive basis.
Lilly Collaboration
In December 2015, the company and Lilly entered into a collaboration and license agreement, under which Lilly has the worldwide license to develop and commercialize products combining the company’s rHuPH20 enzyme with Lilly proprietary biologics. Lilly has the right to select up to three targets. Targets may be selected on an exclusive basis. Lilly has elected two targets on an exclusive basis and one target on a semi-exclusive basis.
BMS Collaboration
In September 2017, the company and BMS entered into a collaboration and license agreement, which became effective in November 2017, under which BMS had the worldwide license to develop and commercialize products combining the company’s rHuPH20 enzyme with BMS products directed at up to eleven targets. Targets may be selected on an exclusive basis or non-exclusive basis. BMS has designated multiple immuno-oncology targets including programmed death 1 (‘PD-1’) and has an option to select three additional targets by November 2024. In October 2019, BMS initiated a Phase 1 study of relatlimab, an anti-LAG-3 antibody, in combination with nivolumab using ENHANZE technology. In May 2021, BMS initiated a Phase 3 of nivolumab using ENHANZE technology for patients with advanced or metastatic clear cell renal cell carcinoma (CheckMate-67T), leveraging data and insights from Phase 1/2 CA209-8KX study in patients with solid tumors. In October 2023, BMS reported positive top-line data from the Phase 3 CheckMate-67T trial evaluating a SC formulation of Opdivo (nivolumab) with ENHANZE in patients with advanced or metastatic clear cell renal cell carcinoma (‘ccRCC’) who have received prior systemic therapy. The study met its co-primary PK endpoints and a key secondary endpoint.
In June 2022, BMS nominated an undisclosed target, which was returned in January 2024. In March 2023, BMS initiated a Phase 3 trial to demonstrate the drug exposure levels of nivolumab and relatlimab fixed-dose combination with ENHANZE is not inferior to IV administration in participants with previously untreated metastatic or unresectable melanoma (RELATIVITY-127).
Alexion Collaboration
In December 2017, the company and Alexion entered into a collaboration and license agreement (‘CLA’), under which Alexion has the worldwide license to develop and commercialize products combining the company’s rHuPH20 enzyme with Alexion’s portfolio of products directed at up to four exclusive targets. Alexion notified the company of a discontinuation of its CLA, effective in the first quarter of 2024.
argenx Collaboration
In February 2019, the company and argenx entered into an agreement for the right to develop and commercialize one exclusive target, the human neonatal Fc receptor FcRn, which includes argenx’s lead asset efgartigimod (ARGX-113), and an option to select two additional targets using ENHANZE technology. In May 2019, argenx nominated a second target to be studied using ENHANZE technology, a human complement factor C2 associated with the product candidate ARGX-117, which is being developed to treat severe autoimmune diseases in Multifocal Motor Neuropathy (‘MMN’). In October 2020, the company and argenx entered into an agreement to expand the collaboration relationship, adding three targets for a total of up to six targets under the collaboration.
In December 2021, argenx announced the FDA approval of efgartigimod (VYVGART) for the treatment of generalized myasthenia gravis (‘gMG’) for the IV dosing regimen. In March 2022, argenx announced that data from argenx’s phase 3 ADAPT-SC study evaluating SC efgartigimod utilizing ENHANZE (1000mg efgartigimod-PH20) for the treatment of gMG achieved the primary endpoint of total IgG reduction from baseline at day 29, demonstrating statistical non-inferiority to VYVGART (efgartigimod alfa-fcab) IV formulation in gMG patients.
In June 2023, argenx received FDA approval under the brand name VYVGART Hytrulo for the injection with ENHANZE for SC use of the treatment of gMG in adult patients who are anti-acetylcholine receptor (‘AChR’) antibody positive. In November 2023, argenx received EC approval of VYVGART SC for the treatment of gMG, which also provides the option for patient self-administration. In January 2024, argenx received Japan approval for VYVDURA (efgartigimod alfa and hyaluronidase-qvfc) co-formulated with ENHANZE for the treatment of adult patients with gMG, including options for self-administration. argenx also expects the regulatory decision on approval of VYVGART SC for gMG in China through Zai Lab by the end of 2024.
In July 2023, argenx reported positive data from the ADHERE study evaluating VYVGART Hytrulo with ENHANZE in adults with CIDP. In February 2024, argenx announced that the FDA had accepted for priority review a sBLA for VYVGART Hytrulo for the treatment of CIDP. The application has been granted a Prescription Drug User Fee Act (‘PDUFA’) action date of June 21, 2024. argenx also expects to submit VYVGART SC for CIDP for regulatory approval in Japan, Europe, China and Canada in 2024. In September 2023, Zai Lab limited (argenx commercial partner for China) announced the CDE of the National Medical Products Administration (‘NMPA’) granted Breakthrough Therapy Designation for efgartigimod SC for the treatment of patients with CIDP.
In November 2023, argenx reported that the ADVANCE-SC study, evaluating VYVGART Hytrulo in adults with primary immune thrombocytopenia (‘ITP’) did not meet the primary endpoint of a sustained platelet count response in chronic ITP patients. In December 2023, argenx reported that the ADDRESS study, evaluating efgartigimod SC in adults with pemphigus vulgaris (‘PV’) and pemphigus foliaceus (‘PF’) resulted in the proportion of PV patients achieving the primary endpoint of complete remission on a minimal dose of steroids (‘CRmin’) was not significantly different between efgartigimod SC and the control arm. In both studies, patients treated with Efgartigimod PH20 SC achieved the same magnitude of total Immunoglobulin G (‘IgG’) reduction as observed in previous clinical trials, reflecting no impact of the route of administration on the study results. argenx will not pursue additional development in pemphigus.
argenx is conducting a Phase 2 study of ARGX-113 (ALKIVIA) using ENHANZE technology for patients with active idiopathic inflammatory myopathy (Myositis) and another study, BALLAD, evaluating ARGX -113 using ENHANZE in bullous pemphigoid. argenx intends to initiate a registrational trial of ARGX-113 using ENHANZE technology for patients with thyroid eye disease in 2024.
Horizon Collaboration
In November 2020, the company and Horizon entered into a global collaboration and license agreement that gives Horizon exclusive access to ENHANZE technology for SC formulation of medicines targeting IGF-1R. Horizon intends to use ENHANZE to develop a SC formulation of TEPEZZA (teprotumumab-trbw), indicated for the treatment of thyroid eye disease, a serious, progressive and vision-threatening rare autoimmune disease, potentially shortening drug administration time, reducing healthcare practitioner time and offering additional flexibility and convenience for patients. In March 2021, Horizon completed dosing in a Phase 1 study exploring the SC formulation of TEPEZZA. The trial was a small, single-dose Phase 1 PK trial which included evaluation of ENHANZE technology for a SC formulation. In March 2022, Horizon announced the completion of a Phase 1 trial for the TEPEZZA SC program. In October 2023, Horizon became an affiliated entity of Amgen Inc. Horizon noticed a return of the target and discontinuation of the company’s CLA, effective in the second quarter of 2024.
ViiV Healthcare Collaboration
In June 2021, the company and ViiV entered into a global collaboration and license agreement that gives ViiV exclusive access to the company’s ENHANZE technology for four specific small and large molecule targets for the treatment and prevention of HIV. These targets are integrase inhibitors, reverse transcriptase inhibitors limited to nucleoside reverse transcriptase inhibitors (‘NRTI’) and nucleoside reverse transcriptase translocation inhibitors (‘NRTTIs’), capsid inhibitors and broadly neutralising monoclonal antibodies (‘bNAbs’), that bind to the gp120 CD4 binding site. In December 2021, ViiV initiated enrollment of a Phase 1 study to evaluate cabotegravir administered subcutaneously with ENHANZE. In February 2022, ViiV initiated enrollment of a Phase 1 study to evaluate the safety and PKs of N6LS, a broadly neutralizing antibody, administered subcutaneously with ENHANZE technology. In June 2022, ViiV initiated enrollment of a Phase 1 single dose escalation study to evaluate PKs, safety and tolerability of long-acting cabotegravir administered subcutaneously with ENHANZE technology. In August 2023, ViiV initiated a Phase 2b study to evaluate the efficacy, safety, PKs and tolerability of VH3810109 (N6LS) administered subcutaneously with rHuPH20 in combination with cabotegravir. In the third quarter of 2023, ViiV initiated a Phase 1 study with ENHANZE for an undisclosed program.
Chugai Collaboration
In March 2022, the company and Chugai entered into a global collaboration and license agreement that gives Chugai exclusive access to ENHANZE technology for an undisclosed target. Chugai intends to explore the potential use of ENHANZE for a Chugai drug candidate. In May 2022, Chugai initiated a Phase 1 study to evaluate the PKs, pharmacodynamics, and safety of targeted antibody administered subcutaneously with ENHANZE.
Acumen Collaboration
In November 2023, the company and Acumen entered into a global collaboration and non-exclusive license agreement that provides Acumen access to ENHANZE for a single target. Acumen intends to explore the potential use of ENHANZE for ACU193, Acumen’s clinical stage monoclonal antibody candidate to target Amyloid-ß Oligomers for the treatment of early Alzheimer’s disease.
Device and Other Drug Product Collaborations
Teva License, Development and Supply Agreements
In July 2006, the company entered into an exclusive license, development and supply agreement with Teva for an epinephrine auto- injector product to be marketed in the U.S. and Canada. The company is the exclusive supplier of the device, which the company developed, for Teva’s generic Epinephrine Injection USP products, indicated for emergency treatment of severe allergic reactions including those that are life threatening (anaphylaxis) in adults and certain pediatric patients. Teva’s Epinephrine Injection, utilizing the company’s patented VIBEX injection technology, was approved by the FDA as a generic drug product with an AB rating, meaning that it is therapeutically equivalent to the branded products EpiPen and EpiPen Jr and therefore, subject to state law, substitutable at the pharmacy.
In December 2007, the company entered into a license, development and supply agreement with Teva under which the company developed and supply a disposable pen injector for teriparatide. Under the agreement, the company is entitled to receive royalties on net product sales by Teva in territories where commercialized.
The company is the exclusive supplier of the multi-dose pen, which the company developed, used in Teva’s generic teriparatide injection product. In 2020, Teva launched Teriparatide Injection, the generic version of Eli Lilly’s branded product Forsteo featuring the company’s multi-dose pen platform, for commercial sale in several countries outside of the U.S. In November 2023, Teva announced FDA approval of the generic version of Forteo, featuring the company’s multi-dose auto-injector pen platform for the treatment of osteoporosis among certain women and men.
Pfizer Agreement
In August 2018, the company entered into a development agreement with Pfizer to jointly develop a combination drug device rescue pen utilizing the QuickShot auto-injector and an undisclosed Pfizer drug. Pfizer has provided the intellectual property rights for further development of the product to the company and has retained an option to assist in the marketing, distribution and sale if the company complete development of the product and submit for regulatory approval. The company is continuing to evaluate the next steps for this program.
Idorsia Agreement
In November 2019, the company entered into a global agreement with Idorsia to develop a novel, drug-device product containing selatogrel. A new chemical entity, selatogrel is being developed for the treatment of a suspected acute myocardial infarction (‘AMI’) in adult patients with a history of AMI.
In January 2024, Idorsia disclosed that recruitment of their Phase 3 study with selatogrel for acute myocardial infarction had reached more than 5,500 patients.
Otter Agreement
In December 2021, the company entered into a supply agreement with Otter to manufacture the VIBEX auto-injection system device, designed and developed to incorporate a pre-filled syringe for delivery of methotrexate, assemble, package, label and supply the final OTREXUP product and related samples to Otter at cost plus mark-up. Otter is responsible for manufacturing, formulation and testing of methotrexate and the corresponding pre-filled syringe for assembly with the device manufactured by the company, along with the commercialization and distribution of OTREXUP. OTREXUP is a SC methotrexate injection for once weekly self-administration with an easy-to-use, single dose, disposable auto injector, indicated for adults with severe active rheumatoid arthritis (‘RA’), children with active polyarticular juvenile idiopathic arthritis and adults with severe recalcitrant psoriasis. Further, the company entered into a license agreement with Otter in which the company granted Otter a worldwide, exclusive, fully paid-up license to certain patents relating to OTREXUP that may also relate to the company’s other products for Otter to commercialize and otherwise exploit OTREXUP in the field as defined in the license agreement.
Patents and Intellectual Proprietary Rights
Halozyme Patent Portfolio
The company’s Halozyme patent portfolio includes patents the company owns solely and, in some cases, jointly with several licensees in the U.S., Europe and other countries in the world; and the company also has numerous pending patent applications. The company has multiple patents and patent applications throughout the world pertaining to the company’s recombinant human hyaluronidase and methods of use and manufacture, including an issued U.S. patent, which expires in 2027, an issued European patent, which expires in 2024, and additional patents that are valid into 2029, which cover the products and product candidates under the company’s existing collaborations and Hylenex recombinant. In addition, the company has, under prosecution throughout the world, multiple patent applications that relate specifically to individual product candidates under development, and jointly owned patent applications relating to the company’s collaborations with several licensees (including, but not limited to, patent applications covering co-formulations and methods of treatment or use that if granted will be valid into the 2040s), the expiration of which can only be definitely determined upon maturation into the company’s issued patents. The company’s patent filings represent a barrier to entry for potential competitors looking to utilize these hyaluronidases, other drugs and drug delivery devices.
Manufacturing
ENHANZE
The company has existing supply agreements with contract manufacturing organizations Avid Bioservices, Inc. (‘Avid’) and Catalent Indiana LLC (‘Catalent’) to produce supplies of bulk rHuPH20. These manufacturers each produce bulk rHuPH20 under current Good Manufacturing Practices (‘cGMP’) for clinical and commercial uses. Catalent produces bulk rHuPH20 for use in Hylenex and collaboration products and product candidates. Avid produces bulk rHuPH20 for use in collaboration products and product candidates. The company relies on their ability to successfully manufacture these batches according to product specifications.
The company has a commercial manufacturing and supply agreement with Patheon Manufacturing Services, LLC (‘Patheon’) under which Patheon will provide the final fill and finishing steps in the production process of Hylenex recombinant.
Devices
Below is a summary of the company’s key production, manufacturing, assembly and packaging arrangements with third-party manufacturers for products commercialized by the company and its partners:
Phillips-Medisize Corporation (‘Phillips’), an international outsource provider of design and manufacturing services, produces commercial quantities of components of the company’s QuickShot auto-injector device for XYOSTED and the company’s VIBEX epinephrine auto-injector product with Teva.
ComDel Innovation, Inc. (‘ComDel’), a domestic provider of integrated solutions for product development, tooling, and manufacturing, produces commercial quantities of components for the VIBEX teriparatide auto-injector product with Teva and the VIBEX auto-injector device for the OTREXUP product for Otter.
Jabil Healthcare, an international manufacturing development company, produces commercial quantities of components of the company’s VIBEX auto-injector device for the OTREXUP product for Otter and the VIBEX epinephrine auto-injector product with Teva.
Fresenius Kabi supplies commercial quantities of pre-filled syringes of testosterone for XYOSTED.
Sharp Corporation (‘Sharp’), an international contract packaging company, assembles and packages XYOSTED auto-injector products and the OTREXUP auto-injector product for Otter.
Sales, Marketing and Distribution
The company has two teams of sales specialists, one that provide hospital and surgery center customers with the information needed to obtain formulary approval for, and support utilization of, Hylenex recombinant and one that supports the promotion of the company’s testosterone product XYOSTED. The company’s commercial activities also include marketing and related services and commercial support services, such as commercial operations, managed markets and commercial analytics. The company also employs third-party vendors, such as advertising agencies, market research firms and suppliers of marketing and other sales support related services to assist with the company’s commercial activities.
The company sells XYOSTED and Hylenex recombinant in the U.S. to wholesale pharmaceutical distributors, who sell Hylenex to hospitals and XYOSTED to other end-user customers. The company engages Integrated Commercialization Solutions (‘ICS’), a division of AmerisourceBergen Specialty Group, a subsidiary of AmerisourceBergen, to act as the company’s exclusive distributor for commercial shipment and distribution of Hylenex recombinant to the company’s customers in the U.S. The company also contracts with numerous wholesale distributors, including Cardinal, McKesson Corporation (‘McKesson’), and AmerisourceBergen Corporation to distribute XYOSTED, to retail pharmacies, as well as the Veterans Administration and other governmental agencies.
In addition to shipping and distribution services, these distributors and third-party logistics providers, Cardinal Health 105, Inc., also known as Specialty Pharmaceutical Services (‘Cardinal’), and Knipper Health, Inc. (‘Knipper’) provide the company with other key services related to logistics, warehousing, returns and inventory management, sales reports, contract administration and chargebacks processing and accounts receivable management. The company also uses a division of Cardinal and Knipper for sample administration. In addition, the company utilizes these third parties to perform various other services for the company relating to regulatory monitoring, including call center management, adverse event reporting, safety database management and other product maintenance services. The company has also contracted with several specialty pharmacies to support fulfillment of certain prescriptions. In addition, the company uses third parties to perform various other services for the company relating to regulatory monitoring, including adverse event reporting, safety database management and other product maintenance services.
Competition
Hylenex Recombinant
The competitors for Hylenex recombinant include Amphastar Pharmaceuticals, Inc.’s product, Amphadase, a bovine (bull) hyaluronidase.
Devices
The company’s competitors include established specialty pharmaceutical companies, major brand name and generic manufacturers of pharmaceuticals, such as Teva, Viatris, Eli Lilly, and Endo. The company’s competitors also include third party contract medical device design and development companies, such as Scandinavian Health Ltd., Ypsomed AG, West Pharmaceutical, and Owen Mumford Ltd.
Government Regulations
The FDA and comparable regulatory agencies in foreign countries regulate the manufacture and sale of the pharmaceutical products that the company or its partners have developed or that the company’s partners are developing.
History
Halozyme Therapeutics, Inc. was founded in 1998.
